OBJECTIVE: To study the possible contribution of paternal, in addition to maternal, carriage of M2/ANXA5 as a risk factor for recurrent pregnancy loss (RPL). DESIGN: Case-control study. SETTING: Academic research center. PATIENT(S): Couples presenting themselves to the Fertility Center, Ludwig-Maximilians-University Munich with two or more consecutive, unexplained miscarriages were selected for this study. Fertile female controls were from the same center and also from the resource of the Institute of Human Genetics, Westfalian Wilhelms-University Muenster. Population controls were drafted from the PopGen biobank, University Clinic Schleswig-Holstein Kiel. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of M2 carriage was estimated in patient and control groups, odds ratios were calculated, and RPL risk was evaluated. RESULT(S): In comparison with female fertile controls, the risk for repeated abortion in the RPL group, associated with M2 carriage, was between 1.7 and 3.8, and it was 2.3 compared with population controls. Because of the equal genetic incidence of M2, with an allelic frequency of 0.167 in the female and male partner RPL subgroups, the haplotype confers approximately the same relative risk to carriers of both sexes. CONCLUSION(S): Paternal M2 carriage seems to confer an equal risk for recurrent miscarriages as M2 carriage in RPL mothers. This finding points to a role of ANXA5 and the M2 haplotype in the fetus and/or the extraembryonic membranes for pregnancy pathology. Prognostic RPL algorithms might be improved by testing the male partner for M2 carriage, and this may guide adequate therapeutic decisions.